The membrane type (MT)-matrix metalloproteinases (MMPs) constitute a sub-group of membrane-anchored MMPs that are major mediators of pericellular proteolysis and physiological activators of pro-MMP-2. MT-MMPs activate the zymogenic form of MMP-2 (pro-MMP-2 or pro-gelatinase A) (Hernandez-Barrantes et al, 2002, Semin. Cancer Biol, 12:131-8; Zucker et al, 2003, Curr Top Dev Biol, 54: 1-74). MMP-2, in turn, can activate pro-MMP-9 (Toth et al, 2003, Biochem Biophys Res Commun, 308:386-95). The MT-MMPs comprise six members of plasma-tethered MMPs, which include four type I transmembrane enzymes (MMP-14, -15, -16, and -24) and two glycosylphosphatidylinositol-anchored enzymes (MMP-17, and -25) (Zhao et al, 2004, J Biol Chem, 279: 8592-8601). In addition to being potent extracellular matrix (ECM)-degrading enzymes, the type I transmembrane MT-MMPs can also initiate a cascade of zymogen activation on the cell surface.